%0 Journal Article
%T Combination Adoptive Cell Transfer Immunotherapy and Chemotherapy in Advanced Triple-Negative Breast Cancer: Phase Ib Results from the ImmunoBreast Trial
%A Jonas T. Fernandez
%A Ana Ferrari
%J Asian Journal of Current Research in Clinical Cancer
%@ 3062-4444
%D 2022
%V 2
%N 1
%R 10.51847/t2UzEYKa2z
%P 153-168
%X Adoptive cellular immunotherapy has emerged as a potential treatment modality for advanced malignancies, yet its broader clinical application is constrained by difficulties in producing large quantities of immune cells with diverse tumor-recognition capabilities. To address this limitation, we developed Autologous Lymphoid Effector Cells Specific against Tumor (ALECSAT), a personalized approach that generates functionally mature, polyclonal lymphocytes from peripheral blood with antitumor activity. This phase Ib, single-institution study explored the safety profile, feasibility, and early signals of clinical benefit associated with ALECSAT administered alongside carboplatin and gemcitabine in patients with locally advanced or metastatic triple-negative breast cancer (mTNBC). A total of fifteen patients diagnosed with mTNBC were enrolled. ALECSAT was infused at 4-week intervals for the first three administrations, followed by maintenance dosing every six weeks. Standard chemotherapy with carboplatin and gemcitabine was delivered on days 1 and 8 of repeated 21-day cycles. Phenotypic characterization of infused cellular products was performed using multiparameter flow cytometry. In parallel, tumor biopsies were used to establish patient-derived xenograft (PDX) models, which were subsequently treated with ALECSAT to evaluate concordance with clinical outcomes. Fourteen patients who had previously undergone one to four systemic treatment regimens received between one and ten ALECSAT infusions. The combined treatment regimen demonstrated acceptable tolerability, with adverse events largely attributable to chemotherapy rather than cell therapy. Frequently reported toxicities included asthenia, gastrointestinal symptoms, and hematologic suppression. Severe adverse events (grade ≥3) were primarily hematologic, consisting mainly of transient neutropenia and thrombocytopenia. Antitumor activity was observed, with one patient achieving complete tumor regression, four exhibiting partial responses, five maintaining disease stabilization, and four experiencing disease progression. The resulting objective response rate was 36% (95% CI 12.8–64.9%). Median progression-free survival was 4.3 months (95% CI 1.6–7.0), while median overall survival reached 8.7 months (95% CI 5.1–12.4). Improved clinical outcomes were associated with higher cumulative numbers of infused ALECSAT cells, particularly cytotoxic CD8⁺ T lymphocytes. Notably, therapeutic responses in patients were reflected by treatment effects observed in matched PDX models. The administration of ALECSAT in combination with platinum-based chemotherapy was feasible and exhibited an acceptable safety profile in patients with mTNBC, with preliminary evidence of antitumor efficacy. These findings provide a rationale for further clinical development of ALECSAT in larger trials.
%U https://galaxypub.co/article/combination-adoptive-cell-transfer-immunotherapy-and-chemotherapy-in-advanced-triple-negative-breast-cmsfxakfigogwps